CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1

Lu, Yeting; Zhou, Shuping; Cheng, Gong; Ruan, Yi; Tian, Yuan; Lv, Kaiji; Han, Shuo; Zhou, Xinhua

doi:10.1155/2022/1911592

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…Another intriguing miRNA is miR-485-5p, which was also found to be lower in tumors with distant metastasis, although it was found to possess a higher expression in patients who did not have a lymphovascular invasion. This miRNA acts as a suppressor of various tumor types, including breast cancer [48][49][50][51], and is also under regulation by upstream competitive endogenous circular and long noncoding RNA molecules [52][53][54][55].…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

Ahram,

Abu Alragheb,

Abushukair

et al. 2024

Cancers

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It is crucial to identify novel molecular biomarkers and therapeutic targets for triple-negative breast cancer (TNBC). The androgen receptor (AR) is a regulator of TNBC, acting partially via microRNA molecules (miRNAs). In this study, we used PCR arrays to profile the expression of 84 miRNAs in 24 TNBC tissue samples, which were equally classified according to AR expression and/or metastasis. Several bioinformatics tools were then utilized to determine the potentially affected protein targets and signaling pathways. Seven miRNAs were found to be significantly more highly expressed in association with AR expression, including miR-328-3p and miR-489-3p. Increased expression of miR-205-3p was found to be significantly associated with metastasis. Certain miRNAs were specifically found to be differentially expressed in either metastatic or non-metastatic AR-positive tumors. A gene ontology (GO) analysis indicated biological roles in the regulation of transcription, cellular response to DNA damage, and the transforming growth factor-beta (TGF-beta) signaling pathway. The GO analysis also showed enrichment in kinase and transcription factor activities. The TGF-beta and a number of kinase-dependent pathways were also retrieved using the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. This study offers an understanding of the role of AR in TNBC and further implicates miRNAs in mediating the effects of AR on TNBC.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

Ahram,

Abu Alragheb,

Abushukair

et al. 2024

Cancers

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“…Interestingly, circFARP1 could enable CAFs to promote GEM resistance in PC via the leukemia inhibitory factor (LIF)/STAT3 axis ( Hu et al, 2022 ). CircLMTK2, an over-expressed circRNA in GEM-resistant PC cells and PC tissues, could contribute to GEM resistance via modulating p21 (RAC1) activated kinase 1 (PAK1) by sponging miR-485-5p ( Lu et al, 2022 ).…”

Section: Circrnas and Drug Resistancementioning

confidence: 99%

Noncoding RNAs: an emerging modulator of drug resistance in pancreatic cancer

Wei

Sun

Wang

et al. 2023

Front. Cell Dev. Biol.

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Pancreatic cancer is the eighth leading cause of cancer-related deaths worldwide. Chemotherapy including gemcitabine, 5-fluorouracil, adriamycin and cisplatin, immunotherapy with immune checkpoint inhibitors and targeted therapy have been demonstrated to significantly improve prognosis of pancreatic cancer patients with advanced diseases. However, most patients developed drug resistance to these therapeutic agents, which leading to shortened patient survival. The detailed molecular mechanisms contributing to pancreatic cancer drug resistance remain largely unclear. The growing evidences have shown that noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are involved in pancreatic cancer pathogenesis and development of drug resistance. In the present review, we systematically summarized the new insight on of various miRNAs, lncRNAs and circRNAs on drug resistance of pancreatic cancer. These results demonstrated that targeting the tumor-specific ncRNA may provide novel options for pancreatic cancer treatments.

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“…For example, hypoxic exosomal HIF-1α-stabilizing circZNF91 promotes chemoresistance of normoxic PC cells via enhancing glycolysis [ 9 ]. Another study reported that circLMTK2 knockdown attenuated GEM resistance of PC cells by regulating PAK1 via miR-485-5p [ 10 ]. Our previous study has revealed the functional profiles of differentially expressed circRNAs associated with GEM resistance in PC cells [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

circACTR2 attenuates gemcitabine chemoresiatance in pancreatic cancer through PTEN mediated PI3K/AKT signaling pathway

et al. 2023

Biol Direct

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Background Recently, accumulating studies have unveiled that circRNAs exert critical function in a variety of tumor biological processes including chemoresistance. Our previous study has found circACTR2 is significantly down-regulated in acquired gemcitabine (GEM)- resistant pancreatic cancer (PC) cells, which has not been well-explored. Our study aimed to research the function and molecular mechanism of circACTR2 in PC chemoresistance. Methods qRT-PCR and western blot analysis was performed to detect gene expression. The effect of circACTR2 on PC GEM resistance were examined by CCK-8 and flow cytometry assays. Whether circACTR2 could sponge miR-221-3p and regulate PTEN expression were determined by bioinformatics analysis, RNA pull-down, and Dual-luciferase reporter assay. Results circACTR2 was notably down-regulated in a panel of GEM-resistant PC cells lines, and negatively associated with aggressive phenotype and poor prognosis of PC. circACTR2 downregulation contributed to GEM chemoresistance of PC cells with decreased S phase ratio of cell cycle and cell apoptosis, as confirmed by gain- and loss-of-function assays in vitro. In addition, circACTR2 overexpression retarded GEM resistance in vivo. Further, circACTR2 acted as a ceRNA against miR-221-3p, which directly targeted PTEN. The mechanistic studies revealed that loss of circACTR2 promoted GEM resistance in PC through activating the PI3K/AKT signaling pathway by downregulating PTEN expression in a miR-221-3p dependent manner. Conclusions circACTR2 reversed the chemoresistance of PC cells to GEM through inhibiting PI3K/AKT signaling pathway by sponging miR-221-3p and upregulating PTEN expression.

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CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1

Cited by 5 publications

References 28 publications

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

MicroRNAs Associated with Androgen Receptor and Metastasis in Triple-Negative Breast Cancer

Noncoding RNAs: an emerging modulator of drug resistance in pancreatic cancer

circACTR2 attenuates gemcitabine chemoresiatance in pancreatic cancer through PTEN mediated PI3K/AKT signaling pathway

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